Organometallic compounds



w th" Patented Dec. 8, 1953 7 UNITED STATES PATENT I jOFF-ICE I assaove i I ORGANOMETALLIC COMPOUNDS Ernst A. H. Friedheim, New York, N. Y. No Drawing. briginalapplicaticn January 28 1947, Serial No. 724,925. Divided and this application June 13, 1951, Serial No. 231,434

This invention relates to organometallic compounds containing radicals of arsenic or antimony and has particular relation to organometallic compounds of this type in which the radicals of arsenic or antimony are linked to sulfur-containing organic radicals. The invention also relates to methods of preparing such compounds.

The main object of the present invention consists in providing organometallic compounds containing radicals of arsenic or antimony, which show valuable therapeutical properties.

Another object of my present invention is to provide organometallic compounds of the abovementioned type which yield injectable, stable solutions.

Other objects and the advantages of the invention will be apparent from the following specification and claims which show, by Way of example, some preferred embodiments of the invention.

Therapeutically useful organometallic compounds of arsenic and antimony in which the arsenic atom orantimony atom is linked to form the grouping I and in which each of the two sulfur atoms is part of an individual -SR radical (mercaptan residue) have been known. These compounds correspond to the general formula Ar.Me=(SR) 2 (I) wherein Ar is an organic radical, Me stands, an atom of trivalent arsenic or antimony,,and SR is the residue of an organic sulfhydril compound. The therapeutically useful organometallic compounds, according to the present invention, contain radicals of trivalent arsenic and antimony in which the arsenic atom or antimony atom is linked to two sulfur atoms which are substituents of the same organic radical, said organometallic compounds corresponding to the general formula I have found that compounds of the above shown general structure (II) have outstanding 2 Claims. (01. 260-242) chemotherapeutic, for example, trypanocidal activity, combined with relatively low toxicity. Furthermore, such compounds are distinguished by their stability. According to the nature of the dimercapto compound used, the final product may have special propertiesofsolubility which.

are highly desirable from the angle of practical medicine. For example, the combination of certain phenylarsenic and phenylantimony compounds with 2,3-dimercaptoprcpanol leads to compounds yielding stable solutions in propylene glycol, while their combination with 2,3-dimercaptopropionic acid leads to water-soluble compounds.

The general method for the preparation of compounds forming the subject of this invention consists of mixing a suitable dimercapto compound with dispersion or solution of an organometallic compound containing trivalent antimony or arsenic linked to a carbon atom. The combination takes place, as a rule, rapidly at room temperature according to the following scheme:

In the above schem R is an organic radical and -MeX stands for a radical of trivalent arsenic ,or antimony, which is capable of reacting with the-'dithiol used. For example, MeX may stand --SbC 12, Sb0, and antimony thiomalate radicals.

The organometallic compound may also be put to the reaction in the pentavalent state, provided conditions are such as to bring about in the reaction mixture a reduction to the trivalent state. This may be obtained by using an appropriate excess of the dimercapto compound which will act as a reducing agent.

If an aqueous reaction medium is used in a reaction with a oiimercapto compound, it is preferable to adjust the pH of the reaction mixture to 6 to 8. The reaction may also be carried out in a non-aqueous medium, for example in alcoholic or glycol solution.

Another procedure to obtain compounds corresponding to the present invention consists in first forminga-compound of the formula s-o: RM! so= and further reacting the compound thus obtained with another suitable organic compound. For example a compound of the formula s-ononzon 4 may be first prepared in the manner described a in detail hereinafter and the compound formed may be reacted with a suitable 1,3,5-triazine halogen derivative to form a compound corresponding to the formula The compounds forming the object ofthisin vention have the following groupproperties;

The nitroprusside reactionfbn-SH groupsais 15? negative or only very faintly positiveeundertclase sical condition, 1. e. in the presence of sodium carbonate at a pI-I of about 3, but becomes positive on addition of caustic alkali, such as NaOI-I, i. e. at a pH of at least 910.'

Theprccedure for the preparation of the compounds eznbodying'the present invention will become more apparent from the following examples.

mammal-56.4 millimols of sodium p-melaminylphenylstihonate (I) are suspended in100 ml. of water, and to this suspension 218 millimole of ammonium thioglycolate, i. e., approximately 6 equivalents based on the amount of '(I) are added in concentrated (50-58%) aqueous solution; The reaction mixtureis stirred at room temperature. for 10 minutes to form a nearly clear, slightly brownish solutionhaving a pHoi about 9;

The pHis' adjusted to 6.5-7 by'addition' of 27 ml. of 20% aqueousacetic acid. The reaction mixture is filtered and the clear filtrate is diluted with 200 ml. of water. 40rnillimols, i. e. 10% excess of the theory, of. 2,3-dimercaptopropanel (II), dissolved in 20 ml. of ethanol, are.

added with rapid stirring to the reaction mixture. Awhite. precipitateis formed immediately, filtered off, washed with 500 ml. of. water, 250

ml. of. ethanol and.25G ml. of ether.. The .washed. precipitate is dried in vacuo over sulfuric. acid.

Theyield amounts 110.92% of the theory.

The product thus obtained is insoluble in .water, alcohol and ether. It. is. soluble. in. propylene glycol to at least.10%.. 'ljhissolutionis stable to heating at a temperature. of 30 C..for at least 3 weeks. Theproduct sintersatlf'lfi C. and melts with decomposition between 175and 200 C. The. aqueous suspension of'the substance reduces Fehling solution slowly on" heating. The nitro-prusside reaction for -SH groups is negative to faintly positive in the presence of sodium carbonate, i. e. at a pH of about 8, but becomes strongly positive on addition of 10% aqueous sodium hydroxide; i. e. at a pH of at least 9-10.

The maximum tolerated'dose in-mice i. p.-, of the substance: administered in propylene glycol solution, amounts to 0.03 g./kg.', while the'mini mum curative dose, i. p., inthe T. equiperdum infection of the mouse amounts to 0.0006 g./l g., in propylene glycol solution. Thus, the therapeutic index amounts to 50.

Formation of the above described substance apparently takes place according to thefollowing scheme:

Thewsame-product (III) may also be obtained by'converting Compound I into the corresponding. derivative containing the -Sb==O radical by reduction and reacting an aqueous suspension of. the reduced compoundat substantially. neutral reaction with the. necessary amount of Compound II.

Example 2.- mol of the hydrochlorideof Samino-l-hydroxy-phenyl arsenoxide are dissolved in 48 ml. of Water and enough sodium carbonate to form a clear solution having a pH of 6.0. With rapid stirring 1.1 ml. of 2,3-dimercapto-propanol (11 millimols) are added. A whitish, gluey precipitate is formed, which changes to-a granular whitepowder upon adlusting the pH' to 715' and continuing stirring for half anhour. The precipitate is filtered'off and washed abundantly with distilled water;

The product thus'obtained has the formula (IV) s-orn It" is insoluble in water, readily soluble. in cold acetone and cold ethanol, and sparingly soluble in cold methanol. It can be recrystallized from boiling methyl alcohol. In order to effect such recrystallization, it is dissolved in 40 ml. of boiling methanol, and the slightly turbid solution is filtered, On coolingthe clear filtrate, a snow- White crystalline precipitate of (IV) is formed, filtered off, Washed with methanol and ether, and dried in vacuo. The compound as well as its hydrochloride salt. is soluble in propylene glyc.ol., Such solution of the salt is distinguished by good stability.

Example. .3. mol of 3-(2',l"-diamino- 1";3,5' triazinyl 6") amino 4 hydroxyphenylarsendichloride of theformula 2 s. on.

prepared as described in my U. S. Patent No. 2,386,204, issuspended in 50 times its weight of water 'with theaddition of {6 mols of sodium carbonate and' to the reaction mixture 11. ml. (lloamillimolslof 2,3-dimercaptopropanol are added with vigorous. stirring. Stirring of the reaction mixture is continued for hour.. The resulting precipitate isfiltered off, washed with water and dried i'nwvacuo.

a The product formed has the structural formula 17TH, 011 N N we mac \N% 's-cm S--CH.CH2OH It is insoluble in cold water, and soluble in propyl n y l- V Example 4.--%6 mol of p-aminophenyl arsendi chloride of the structural formula prepared according to known methods, is suspended in 40 times its weight of water and T mol of sodium carbonate, and 11 ml. (116 millimols) of 2,3-dimercapto-propanol are added with vigorous stirring. Stirring is continued for 45 minutes. The precipitate formed, which is filtered off and washed with water, corresponds to the formula It yields injectable solutions in propylene glycol and is soluble in dilute hydrochloric acid.

Example 5.- 6 mol of B-acetylaminol-hydroxy-phenyl-arsenoxide of the formula AsO NH.OOCH| NH.COCH3 The starting material used in this example is prepared by reduction of 3-acetylami'nol-hydroxyphenylarsonic acid according to classical methods with sulfur dioxide in the presence of catalytic quantities of hydriodic acid,

Example 62-1- mol of Z-hydroxy--acetylamino-benzene-arsendichloride of the formula NELQOOE: v is suspended in 50 times its weight of water, and

to the suspension mols of sodium, carbonate and 11 ml. millimols) of 2,3-dimercapto propanol are added with rapid stirring. The resulting precipitate is filtered ofi, washed with water and dried in vacuo.

The reaction product thus formed has the structural formula NELCOCH:

The compound is insoluble in water, soluble in propylene glycol, ethylene glycol, glacial acetic acid, and hot ethanol.

Example 7.-30 millimols oi the mcnosodium salt of 4-carbamidophenylarsonic acid of the formula I As OaH.Na

NHC ONH:

are suspended in 400 m1. of water, and a concentrated (50%) aqueous solution of millimols of ammonium thioglycolate is added. The reaction mixture is stirred in an inert atmosphere at a temperature of 80 0., for 60 minutes. To the resulting solution are added drcpwise with rapid stirring 33 millimols of 2.3-dimercapto propanol. A white precipitate separates from the solution, which is filtered off, washed with water, and dried in vacuo.

The compound formed corresponds to th formula NH.C ONE:

The compound is insoluble in water, chloroform and ether, soluble in propylene glycol.

Example 8.-36.4 vrnillirnols of sodium N-phenylglycineeamide -p-arsonate of the formula 1X5 0 sELNH.

NH.CHzC ONH:

are dissolved in 500 ml. of water. To this solution a 29% aqueous solution of 218 millimcls of sodium thiomalate is added, and the reaction mixture is stirred at room temperature for 60 minutes in an inert atmosphere. To the result.- ing solution 40 millimols of 2,3-dimercaptopropanol dissolved in 2d mluoi ethanol are added with rapid stirring. The whitish precipitate formed is filtered on, and washed with water.

aceaoro 7 The compoundformed.has'the-following str'uetural formula:

' seem A; \S-CH.-OHQQH ilnromoori-m It is insoluble in water and soluble in propylene glycol.

Example 9.-36.4 millimols of the monosodium salt of 4-hydroxypropylaminophenyl-l-arsonic acid of the formula NaHO'QAsONH(OHQ)-2CHaOH If inthe above example instead of the sodium salt of 4.=hydroxypropylaminophenylel-arsonic acid, an equivalentamountof themonosodium salt. of 4-hydroxyethylaminophenyl -l arsonic acid is used under otherwise similar conditions,

acompound corresponding to the following for.-

mula is obtained:

HOHzO.HO-S

The product is insoluble in water. It is soluble in propylene glycol and hot ethanol.

Example 10.-To a aqueous solution containing 50 millimols of sodium p-aminophenylstibonate of the formula HzN.CeI-I4.SbO (OH) ONa) a aqueous solution of'300 millimols of potassium thioglyoolate are added at room tempera ture with rapid stirring, which is continued for about 1 hour. To the resulting clear solution 55' millimols of 2,3-dimercaptopropanol, dissolved in 20 ml. of ethanol are added with constant vigorous stirring. The reaction product separates from the solution in form of a brownish gummy precipitate which is filtered off, and washed with water. The compound formed has the. formula It is insoluble in water but soluble in propylene glycol and sulfuric acid.

Example 11 .To' a 2% aqueoussolution containing 40 millimols of the sodium acetylaminophenylstibonate of the formula CH3.CO.NH.CeH4.SbO (OH) (ONBJ a aqueous solution containing- 240 millimols 8; of; ammonium thioglycolate are. added. at. room temperature with rapid stirring. The stirring is continued for 30 minutes. To the resulting solution 45 millimols of 2,3edimercaptopropanol are added with vigorous stirring. A precipitate is formed, which is filtered off and washed with water. The compoundformed has the formula O 0111.0 ONH Sb S-GH. CHzOH It is insoluble in water. Injectable solutionsmay beprepared. by dissolving theproduct in warm propylene glycol..-

A compound of the formula S-CHz omo'oNH- s I S-CELGHOH may be obtained by a procedure substantially identical with that described above, if an equivalent amount of sodium 3-chloro-4-acetylaminophenylstibonate is substituted for the monosodium-p-aoetylaminophenylstibonate in the above example.

Example 12.3'6.4 millimols of the disodium salt of s-di-plienylcarbamide-4A-distibonic acid, of the formula.

are added to a solution of 218'mi1limols of sodium thioglycolate in 1 liter of water with rapid stirring at room temperature; The stirring is continued for 30 minutes. To the solution thus formed,

' millimols of 2,3-dimercaptopropano1 are added dropwise with. rapid stirring. ,A precipitate is formed which is: filtered off and washed with water.

The reaction product formedhas the formula s-oilomon S-CH:

The product is insoluble in water, but soluble in propylene glycol.

Example 13.To T 6 mol of p-aminophenyl-arsenoxide of the formula suspended in l literofwater. are added 110. millie mols .of. 2,3-dimercaptopropanol dissolved. in. 50 ml. of .ethanolwith rapid stirring. Stirring is continued for. 1 hour. The resulting product has the formula.

S-CH:

ENG-A4 This product, which is identical with that obtained in Example 4, is washed with'water and is then reacted with an aqueous suspension of 1% mol of 2,4-diamino-6-chloroe1,3,5-triazine with stirring at a temperature of. C. at a-pH of 2-4. The

. *9 resulting reaction product corresponds to the formula It is insoluble in Water, cold ethanoland methanol, but soluble in propylene glycol.

Example 14.%6 mol of a compound corresponding to the formula NHr rapid stirring at ordinary room temperature.

Stirring is continued for 20 minutes and the precipitate formed is filtered off, and washed with water. The compound thus formed is identical with that obtained in Example 13.

Example 15. mol of p-hydroxyphenyl arsenoxide of the structural formula is suspended in 50 times its Weight of water and 11 ml. (110 millimols) of 2,3-dimercaptopropanol are added to the solution with vigorous stirring. After 50 minutes of continued stirring the compound iormed is filteredoff and washed with Water. The reaction product, which is soluble in propylene glycol, corresponds to the formula I Example 16.-36.4 millimols of sodium p-melaminylphenylstibonate are suspended in 100 ml. of water and to this solution. 218 millimols of ammonium thioglycolate are added in a 55% aqueous solution. The reaction mixture is stirred at room temperature for minutes to form a solution having a pH of about 9. The pH is adjusted to 6.5-7 by the addition of aqueous acetic acid, the reaction mixture is filtered and the clear filtrate is diluted with 200 ml. of water. 40 millimols of 1,2-prcpanedithiol are now added to the solution with rapid stirring. A white precipitate is formed which is filtered off, washed with water, and dried in vacuo over concentrated sulfuric acid.

In the above example, equivalent amounts of ethanedithiol (SI-LCI-IaCI-IZSH) or 2,3butane dithiol may be substituted for the 1,2-propanedithiol. The dithiols mentioned in this example may be prepared according to the methods described in the U. S. Patent 2,402,643, granted to W. A. Lazier et al. Y

Example 17.- /1o0 mol of the hydrochloride of 3-amino-4.-hydroxyphenylarsenoxide and the requisite amount of sodium carbonate are dissolved in 48 ml. of water to form a clear solution having a pH. of 6.0. To the solution 11 millimols of 1,2- propanedithiol are added with rapid stirring, and stirring is continued for half an hour. A white ued for about minutes.

i0 precipitate is formed which is filtered offand washed with distilled water.

By substituting equivalent amounts of 1,2- ethanedithiol or 2,3-butanedithiol for the 1,2- propane dithiol used in this example, and proceeding in a substantially identical manner, corresponding derivatives containing ethanedithiol and 2,3-butanedithiol, respectively, are obtained.

Example 18.--To an aqueous suspension of 36.4 millimols of sodium p-znelaminylphenylstibonate in ml. of water, a' 55% aqueous solution of 218 millimols of ammonium thioglycolate is added with stirring for about 10 minutes. The pH of the solution is adjusted to 6.5-7 by the addition of dilute aqueous acetic acid. The reaction mixture is filtered and the clear filtrate is diluted with 200 ml. of water. To the diluted solution 40 millimols of 1,3-dithioglycerol are added with rapid stirring. A whitish precipitate is formed which is filtered off, washed with water, and dried in vacuo over concentrated sulfuric acid.

Example 19.To a solution consisting of {V mol of the hydrochloride of 3-amino-4-hydroxyphenylarsenoxide and the requisite amount of sodium carbonate to yield a pH of S in 480 ml. of water, millimols of 1,3-dithioglycerol are added with vigorous stirring. A gluey precipitate is formed which changes to a white powder upon adjusting the pH to 7.5 and continued stirring for half an hour. The precipitate is filtered ofi, washed with water and dried preferably under vacuum in the presence of concentrated sulfuric acid.

Example 20.To a 5% aqueous solution con- I taining 36.4 millimols of sodium p-aminophenylstibonate, a 20% aqueous solution of 218 millimols of potassium thioglycolate are added at room temperature With rapid stirring which is contin- 40 millimols of 1,2- propanedithiol are added with vigorous stirring. The resulting precipitate is filtered off, washed with Water, and dried under vacuum in the presence of concentrated sulfuric acid.

Analogous compounds may be obtained by sub-' and 200 millimols of sodium carbonate and 110 millimols of 1,2-propanedithiol are added with vigorous stirring which is continued for 60 minutes. The reaction product formed is filtered off, washed with water, and dried under vacuum.

Analogous compounds may be obtained by proceeding in substantially the same manner as set forth in the above example, by substituting an equivalent amount of LZ-ethanedithiol or 2,3-butanedithiol for the 1,2-propanedithiol used.

Example 22.-36.4 millimols of sodium p-melaminylphenylstibonate are suspended in 100 ml. of water and to this suspension 218 millimols of potassium thioglycolate are added with stirring.

in 20% aqueous solution. Stirring is continued for 10 minutes and the pH of the reaction mixture is then adjusted to 6.5-7 by the addition of dilute aqueous acetic acid. After filtration, the reaction mixture is diluted with 300 ml. of water and to the-diluted solution 40 millimols of 1,2-dimercaptobenzene, dissolved in alcohol, are added with rapid stirring. The precipitate formed'is fil tered off, and washed abundantly with water.

The washed precipitate is dried in vacuo ove concentrated sulfuric acid.

sesame Example. 3-71 a e r- 91 s sq i iipn. consistin of 3614' millimols of sodium p rnelarninylplienyl stibonate and 100 ml. of water, 21 8 millimols of potassium thioglycolate are' added in 20 aqueous solution and the reaction mixture is stirred at room temperature for 10 minutes The pl-l is adjusted 6.5-7 by the addition of dilute aqueous acetic acid. The reaction mixture is filteredjthe filtrate is diluted with 300 m1. of water andto the diluted liquid 40 millimols of dithio-o-"xylylene glycol of the formula C6H4(CH2SH),2, dissolved in alcohol, are added with rapid stirring. A whitish precipitate is formed which is filtered oft, Washed with water, and dried in vacuo over con: centrated sulfuric acid. Example 24.-To a neutral solution prepared by dissolving 100.millimols of the hydrochloride of 3'-amino l-hydroxyphenylarsenoxide and the requisite amount of sodium carbonate in 480 m1.

of water, 110 millimols'of 1','2-'dimercaptoben fzene, I

dissolved in ethyl alcohol, are added with rapid stirring, whereupon a whitish precipitate is formed. Stirring is continued for abouthalf an hour. The precipitate is'filtered off, washed with distilled water, and dried, preferablyin vacuo iri the presence of concentrated sulfuric acid.

Example 25.To a neutral solution prepared by dissolving 100 millimols of the hydrochloride of 3-amino-4-hyd1oxyphenyl arsenoxide and the requisite amount of sodium carbonate. in 40 ml. of water, 110 millimols of dith'io-o-igylyleneglycol, dissolved in ethyl author are added with rapid stirr'n'g, whereupon a' whitish precipitate formed. Stirring is continued for about half an hour. "The precipitate is filtered off, washed with distilled water and dried, preferably in vacuo in the presence of concentrated sulfuric acid.

' Example 26.l millimols of sodium p-melaminyl-phenylstibonate are dissolved in 19 parts by'weightof propylene glycol. H t v 7 2,3-dimercaptopropanol are added. The, resulting solution is poured with stirring into 1 volumes of water; The precipitate which is. formed iscentrifuged 01f, washed'iwith 'water'and alcohol and dried in vacuo.' The "reaction product is identicalwith the one obtained byftheinethod of Example 1.

For practical therapeutic purposes, it is not necessary to'isolate the" coinpound'but thesolu; tion described above containing in. propylene gly; col as" a solvent the ieaction'product of. sodium p-melaminyl-phenylstibonate and,"2,3dimercaptopropanol in a molar ratioof' 1 'mol cuneiform: to not less than 2 mols or the latter,"'ca'ri' be used directly for parenteral treatment; W

Example 27.-20 millimols of sodium p-acetylaminophenylstibonate are added to a solution of. 100 millimols of ammonium thioglycolate in 250' ml, of Water. The reaction mixture isstir'red for 15 minutes giving a clear solution of 'pH9. alcoholic solution of 22 millimols of 'dithiopentaerythritol, prepared' according to S; P. 2,402,665, is added dropwise with rapid'stir'ring. The resulting precipitate is filtered ofi, washed with water, and dried in vacuo. The product has the formula:

fear. ees. omcoNH-Ose /OK i i i see; onion It is insoluble inwater butv soluble in propylene glycol.

ExampZe ,28.T,o a suspension of.36.4 millimols sodium p-melaminy1phenystibonate 7111300 .1111. of

22 millimols of Itis insoluble in water, alcohol and ether. It is soluble 'waterupon addition ofsodiurh carbonate to yield clear, injectable solutions.

Example. 29. mol ofa compound cortex sponding to the formula 11TH: o

is dissolved in water and to the, rfisulting solution millimols or 'zgs-dimercaptd m i ethyl eth are added with vigorous stirring; A white precipitate forms immediately. ""Itis filtered ofi, washed with water, anddrie'd inyacuofThe product has he ir el te;

It is insoluble in water, but soluble in propylene glycol on warming.

Example 30.-, 10- millimols of p-aminophenylarsenoxide are suspended in enough water to form a 1,% suspension. On addition chem-aqueoussolution of 2,3-dimercaptopropanol:glucoside,

a clear solution results. By evaporatingv this solution, first. underreduced pressure at a tem: perature below 35., and finally invacuooverconcentrated, sulfuric acid, av product is. obtained which, has the following, structure:

It is. insoluble in, ether, chloroform, .andhen.

zene. It'is soluble in water to form injectable solutions.

For practical purposes, it is not necessary. to isolate the product, but thesolution described above containing, in an aqueous medium, the reaction product of p-aminophenylarsenoxide and an equivalent amountof 2,3-dimercaptqpropanolglucoside is suitable. for parenteral administration.

Example 31.To a 5% aqueous, solutioncon; taining 50 millimolsof sodium p-aminophenylstibonate, a 20% aqueous solution o f-3 00 n 1illi.-

mols of potassium thiog lycolate are added at room temperature, with rapid stirring which is continuedfor one hour.

To the resulting solu-. tion, 55 millimols of1,3-disulfhydrylbenzene ,dis:. solved in ethanolareadded with constant vig0r.-.

13 ous stirring. The reaction product separates from the solution, is filtered off and washed with water.

Example 32.0.1 mol of sodium arsanilate is dissolved in 50 parts its weight of water. 22 millimols of 2,3-dimercaptopropanol are added, and the reaction mixture is stirred for 40 minutes at 80 in an inert atmosphere. Stirring is continued for 1 hour at room temperature. The precipitate formed is centrifuged off, washed with water and recrystallized out of boiling methanol. The resulting white crystalline product corresponds to the formula s-om NHPQAS SCHOHzOH It is insoluble in cold water, soluble in hot alcohol, dilute hydrochloric acid and propylene glycol.

As shown in the above examples, the present invention may be applied to various organometallic compounds and various dithiols in order to obtain new compounds embodying the present invention.

The preferred dithiol used in carrying out the present invention is 2,3-dimercaptopropanol. However other dithiols of aliphatic or aromatic compounds, particularly aliphatic and aromatic orthodithiols, may also be used.

Furthermore, in the above described examples, in which thioglycolates are first reacted with the organometallic compounds, and the reaction products formed are further reacted with dithiols, other thio-acid derivatives, such as thiolactates, may be substituted for the thioglycolates.

It is to be understood that in the present specification and claims the term amino radical is used to include NH2 radicals as well as the above disclosed substituted amino radicals. The abbreviation i. p. is used in this specification to denote intra-peritoneal.

It will be apparent from the above description compound of the N -CW N S- H.CH2OH 2. As a new therapeutically active product, an organometallic compound corresponding to the general formula wherein X stands for one of the radicals CI-I2OH and COOH.

ERNST A. H. FRIEDHEIM.

References Cited in the file of this patent UNITED STATES PATENTS Name Date Brown et al Dec. 31, 1940 OTHER REFERENCES Brown et al.: J. Am. Chem. 800., vol. 63, pp. 2054-5 (1941).

Gammill et al.: Chem. Abstracts, vol. 41, p. 2492 (1947).

Number 

2. AS A NEW THEREAPEUTICALLY ACTIVE PRODUCT, AN ORGANOMETALLIC COMPOUND CORRESPONDING TO THE GENERAL FORMULA 